Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
College of Pharmacy, Keimyung University, Daegu 704-701, South Korea.
Arch Biochem Biophys. 2014 Oct 1;559:38-45. doi: 10.1016/j.abb.2014.05.016. Epub 2014 May 26.
Exposure to ultraviolet B (UVB) radiation, a complete environmental carcinogen, induces oxidative and inflammatory skin damage, thereby increasing the risk of skin carcinogenesis. The antioxidant and anti-inflammatory activities of a wide variety of plant polyphenols have been reported. Rutin (3-rhamnosyl-glucosylquercetin), a polyphenol present in many edible plants, possesses diverse pharmacological properties including antioxidant, anti-inflammatory, antimutagenic and anticancer activities. The present study was aimed to investigate the effects of rutin on UVB-induced inflammation in mouse skin in vivo. Topical application of rutin onto the dorsal skin of female HR-1 hairless mice 30 min prior to UVB irradiation diminished epidermal hyperplasia and the levels of proteins modified by 4-hydroxynonenal, which is a biochemical hallmark of lipid peroxidation. Topical application of rutin also significantly inhibited UVB-induced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), two representative inflammatory enzymes, in hairless mouse skin. Rutin inhibited the DNA binding of activator protein-1 (AP-1) and phosphorylation of signal transducer and activator of transcription-3 (STAT3) in mouse skin exposed to UVB. Moreover, rutin attenuated UVB-induced phosphorylation of p38 mitogen-activated protein (MAP) kinase and c-Jun-N-terminal kinase (JNK). Pharmacological inhibition of p38 MAP kinase and JNK decreased UVB-induced expression of COX-2 in mouse skin. Taken together, these findings suggest that rutin exerts anti-inflammatory effects in UVB-irradiated mouse skin by inhibiting expression of COX-2 and iNOS, which is attributable to its suppression of p38 MAP kinase and JNK signaling responsible for AP-1 activation.
暴露于紫外线 B（UVB）辐射，一种完全的环境致癌物，会导致氧化和炎症性皮肤损伤，从而增加皮肤致癌的风险。多种植物多酚具有抗氧化和抗炎活性。芦丁（3-鼠李糖苷葡萄糖基槲皮素）是许多食用植物中存在的一种多酚，具有多种药理作用，包括抗氧化、抗炎、抗突变和抗癌活性。本研究旨在研究芦丁对体内 UVB 诱导的小鼠皮肤炎症的影响。在 HR-1 无毛小鼠背部皮肤涂抹芦丁 30 分钟后，再进行 UVB 照射，可减轻表皮增生和 4-羟基壬烯醛修饰蛋白的水平，后者是脂质过氧化的生化标志。芦丁还可显著抑制 UVB 诱导的无毛小鼠皮肤中环氧化酶-2（COX-2）和诱导型一氧化氮合酶（iNOS）的表达，这两种酶是两种代表性的炎症酶。芦丁抑制了暴露于 UVB 的小鼠皮肤中激活蛋白-1（AP-1）的 DNA 结合和信号转导和转录激活因子 3（STAT3）的磷酸化。此外，芦丁可减弱 UVB 诱导的丝裂原活化蛋白激酶 p38（MAPK）和 c-Jun-N-末端激酶（JNK）的磷酸化。p38 MAPK 和 JNK 的药理学抑制可降低 UVB 诱导的小鼠皮肤中 COX-2 的表达。综上所述，这些发现表明芦丁通过抑制 COX-2 和 iNOS 的表达发挥抗炎作用，这归因于其抑制了负责 AP-1 激活的 p38 MAPK 和 JNK 信号。
